Effect of serine proteinase inhibitors on neutrophil function: alpha-1-proteinase inhibitor, antichymotrypsin, and a recombinant hybrid mutant of antichymotrypsin (LEX032) modulate neutrophil adhesion interactions.
Circulating serine proteinase inhibitors (serpins) regulate a number of proteinases that participate in the inflammatory process. In this study, we investigated possible modulatory effects of serpins on neutrophil adhesion. Antichymotrypsin (ACT), alpha1-protease inhibitor (alpha1-PI), and LEX032, a recombinant hybrid of ACT and alpha1-PI were shown to inhibit neutrophil adhesion to fibronectin (FN)-coated surfaces and, to a lesser extent, adhesion to other extracellular matrix proteins. The inhibitory effect of serpins on neutrophil adhesion to FN was found to be related to inhibition of FN proteolysis based on the following observations: (1) elastase treatment of FN-coated plates, but not of neutrophils, resulted in enhanced neutrophil adhesion; and (2) serpins inhibited FN proteolysis by neutrophil proteases. Serpins also inhibited neutrophil spreading, as well as shedding of neutrophil CD43, but not L-selectin, CD18, or CD29. We conclude that serpins modulate neutrophil adhesion both by inhibiting proteolytic processing of extracellular matrix proteins and proteolytic shedding of CD43.
Carney
D F
DF
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Jagels
M A
MA
Hugli
T E
TE
Sands
H
H
Rubin
H
H
D015703:Antigens, CD; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005139:Eyeglasses; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D051917:Leukosialin; D018375:Neutrophil Activation; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D012795:Sialoglycoproteins / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000502:physiology*
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D051917:Leukosialin; D011994:Recombinant Proteins; C465014:SPN protein, human; D015842:Serine Proteinase Inhibitors; D012795:Sialoglycoproteins; D000515:alpha 1-Antitrypsin; D002918:Chymotrypsin